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The role of variation in the filaggrin gene for the uptake of chemicals via the skin

nte Paoula, Eleni Korre (2019) MOBN03 20182
Degree Projects in Molecular Biology
Popular Abstract
The filaggrin gene and the dermal absorption of chemicals

Filaggrin is a monomeric protein highly expressed in the outer layer of the epidermis and important for building up the skin barrier. About 7-10% of the European popula-tion have a loss-of-function mutation (so called null mutation) in the filaggrin gene (FLG), which leads to a reduction or loss of the filaggrin protein.

The aim of this study was to elucidate whether FLG null mutations and FLG copy number variation affect the absorption of chemicals through the skin and the rise of exposure-related health effects such as oxidative stress and genotoxicity (DNA dam-age). A screening of the population was done to identify individuals with different FLG status, and 23 individuals... (More)
The filaggrin gene and the dermal absorption of chemicals

Filaggrin is a monomeric protein highly expressed in the outer layer of the epidermis and important for building up the skin barrier. About 7-10% of the European popula-tion have a loss-of-function mutation (so called null mutation) in the filaggrin gene (FLG), which leads to a reduction or loss of the filaggrin protein.

The aim of this study was to elucidate whether FLG null mutations and FLG copy number variation affect the absorption of chemicals through the skin and the rise of exposure-related health effects such as oxidative stress and genotoxicity (DNA dam-age). A screening of the population was done to identify individuals with different FLG status, and 23 individuals with and 31 without selected FLG null mutations were cho-sen to undergo a controlled skin exposure of three different chemicals present in the general environment and with low toxicity.

There were 432 individuals that participated in the screening and about 6.5% had one of the FLG null mutations, slightly lower than the European population. FLG has a copy number variation, from 10 to 12 filaggrin repeats. In the 54 selected participants, the distribution of the repeats was similar to what was reported before, with the 11th repeat being the most common among participants, followed by 10th and 12th repeats. We combined carrying FLG null mutations with the presence or absence of the 12th repeat, which was hypothesised to have a protective effect.

Participants with FLG null had higher values of chemical excretion in urine than partic-ipants without the mutation, although not significant. This suggests that participants with the FLG mutation had a higher uptake of the chemicals through the skin, which were excreted in urine. Participants carrying FLG null and absence of 12th repeat had a higher absorption of the chemicals than participants carrying FLG null and presence of 12th repeat or carrying no FLG null mutation and absence of 12th repeat. This indicates that the 12th repeat may also play a role in the chemical absorption through the skin.

We also analysed biomarkers for genotoxicity and oxidative stress in samples before the exposure. Telomere length is found in the end of chromosomes and is shortened with age. It is a biomarker for genotoxicity, since having an abnormal shortening of telo-meres could lead to cancer. FLG mutations were not associated with telomere length in our study. Mitochondria DNA (mtDNA) is a biomarker of oxidative stress. If the cell undergoes oxidative stress, the copy number of mtDNA diminishes with time. In our study, participants carrying the 10th repeat had non-significantly lower copy number of mtDNA, which was hypothesised to be less protective against chemical absorption.

This study increases the knowledge about individual susceptibility to exposure to chemicals via the skin. It may help improve the life and health of FLG null carriers and also aid with prevention of related illness to these compounds.

Master’s Degree Project in Molecular Biology 60 credits 2019
Department of Biology, Lund University
Advisor: Karin Broberg and Karin Wahlberg
Division of Occupation and Environmental Medicine (Less)
Please use this url to cite or link to this publication:
author
nte Paoula, Eleni Korre
supervisor
organization
course
MOBN03 20182
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8995160
date added to LUP
2019-09-17 09:31:36
date last changed
2019-09-17 09:31:36
@misc{8995160,
  author       = {{nte Paoula, Eleni Korre}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The role of variation in the filaggrin gene for the uptake of chemicals via the skin}},
  year         = {{2019}},
}